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Biology subjects

Daly, N. L.

Publications and source records attributed to Daly, N. L..

3 recordsLinked to original sources

Plant Molecules Protect Against Inflammatory Bowel Disease by Restoring Gut Microbiota-Immune Homeostasis and Suppressing Pro-inflammatory Markers

Inflammatory bowel disease (IBD) is associated with chronic intestinal inflammation and gut microbial dysbiosis, yet effective microbiome-targeted therapeutics remain limited. Here, we investigated the anti-inflammatory and microbiome-modulating activities of metabolites isolated from Garcinia brassii, an endemic species of the Australian Wet Tropics. Five compounds, including a new natural product named garcitine, were isolated and structurally characterised. In human immune cells, garcinol and garcinia biflavonoid 1 significantly suppressed lipopolysaccharide-induced production of IL-1{beta}, IL-6, and TNF without detectable cytotoxicity, while parvifoliol F selectively inhibited IL-1{beta} release. Therapeutic efficacy was further evaluated in a TNBS-induced murine colitis model, where garcinia biflavonoid 1 and parvifoliol F significantly reduced colonic inflammation and improved histopathological outcomes. 16S rRNA sequencing demonstrated that both compounds restored gut microbial homeostasis by reversing colitis-associated dysbiosis and reducing inflammation-associated microbial signatures. Functional pathway prediction further suggested suppression of pro-inflammatory microbial metabolic pathways following treatment. Together, these findings demonstrate that Garcinia-derived metabolites alleviate experimental colitis through coordinated immunomodulatory and microbiome-reprogramming mechanisms and identify garcinia biflavonoid 1 and parvifoliol F as promising candidates for microbiome-targeted IBD therapeutics.

immunology↗

ampir: an R package for fast genome-wide prediction of antimicrobial peptides

SummaryAntimicrobial peptides (AMPs) are key components of the innate immune system that protect against pathogens, regulate the microbiome, and are promising targets for pharmaceutical research. Computational tools based on machine learning have the potential to aid discovery of genes encoding novel AMPs but existing approaches are not designed for genome-wide scans. To facilitate such genome-wide discovery of AMPs we developed a fast and accurate AMP classification framework, ampir. ampir is designed for high throughput, integrates well with existing bioinformatics pipelines, and has much higher classification accuracy than existing methods when applied to whole genome data. Availability and Implementationampir is implemented primarily in R with core feature calculation methods written in C++. Release versions are available via CRAN and work on all major operating systems. The development version is maintained at https://github.com/legana/ampir Contactlegana.fingerhut@my.jcu.edu.au; ira.cooke@jcu.edu.au Supplementary informationSupplementary data are available at https://github.com/legana/amp_pub

bioinformatics↗

Hookworm-derived small molecule extracts suppress pathology in a mouse model of colitis and inhibit secretion of key inflammatory cytokines in primary human leukocytes

Iatrogenic hookworm therapy shows promise for treating disorders that result from a dysregulated immune system, including inflammatory bowel disease (IBD). Here we use a metabolomics approach to characterize the non-protein small molecule complement of hookworms. Gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry analyses of somatic tissue extracts revealed the presence of 52 polar metabolites and 22 non-polar components including short chain fatty acids (SCFA). Several of these small metabolites, notably the SCFA, have been shown to have anti-inflammatory properties in various diseases, including IBD. Using a murine model of colitis and human peripheral blood mononuclear cells, we demonstrate that somatic tissue extracts of the hookworm Ancylostoma caninum contain small molecules with anti-inflammatory activities. Of the five extracts tested, two of them significantly protected mice against T cell-mediated immunopathology and weight loss in a chemically-induced colitis model. Moreover, one of the anti-colitic extracts suppressed ex vivo production of inflammatory cytokines from primary human leukocytes. While the origin of the SCFA (parasite or host microbiota-derived) present in the hookworm somatic tissue extracts cannot be ascertained from this study, it is possible that A. caninum may be actively promoting an anti-inflammatory host microbiome by facilitating immune crosstalk through SCFA production.

microbiology↗